Treating non-motor symptoms of Parkinson’s disease with transplantation of stem cells

Abstract

Parkinson’s disease (PD) treatment-based research has focused on developing therapies for the management of motor symptoms. Non-motor symptoms do not respond to treatments targeting motor deficits, thus necessitating an urgent need to develop new modalities that cater to both motor and non-motor deficits. Stem cell transplantation is potentially therapeutic for PD, but the disease non-motor symptoms have been primarily neglected in such cell therapy regimens. Many types of stem cells are currently available for transplantation therapy, including adult tissue (e.g., bone marrow, placenta)-derived mesenchymal stem cells. The fact that mesenchymal stem cells can replace and rescue degenerated dopaminergic and non-dopaminergic cells suggests their potential for the treatment of motor as well as non-motor symptoms of PD, which is discussed in this article.

Keywords:

• mesenchymal stem cells
• motor symptoms
• non-motor symptoms
• Parkinson’s disease
• stem cell therapy

Financial & competing interests disclosure

CV Borlongan is supported by National Institutes of Health, National Institute of Neurological Disorders and Stroke 1R01NS071956–01, Department of Defense W81XWH-11–1–0634, and the James and Esther King Foundation for Biomedical Research Program 1KG01-33966. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• The ideal approach for the treatment of Parkinson’s disease (PD) would be a restorative therapy, which is able to replace the disease-denervated dopaminergic network in an effort to, at the very least, retard the disease progression.

• While restoring the dopamine neuronal circuitry and replacement of dead/dying dopaminergic cells may seem a logical tactic, such a method appears to cater only to motor symptoms of PD. Therefore, a cell-based therapy targeting the non-dopaminergic system underlying non-motor symptoms of PD remains to be explored.

• Somatic cell reprogramming allows generation of human pluripotent stem cells from PD patients and may permit correction of the mutations associated with PD pathology.

• Embryonic stem cells are one type of stem cells which are pluripotent and proliferate indefinitely in culture; however, there is an ethical controversy surrounding embryonic stem cells, similar to the use of fetal tissues, thus making them widely inaccessible.

• Grafted mesenchymal stem cells (MSCs) may retain their stromal cell phenotype (i.e., MSCs) and afford therapeutic benefits via the by-stander mechanism that involves secretion of neurotrophic, neurogenic, angiogenic, vasculogenic and synaptogenic factors.

• MSC may alleviate non-motor PD symptoms by various mechanisms, including via new neuritic outgrowth and formation of synapses, as well as through modulation of a favorable environment for the preservation of host tissue under disease conditions.

• MSCs’ ability to differentiate into a variety of neuronal phenotypes, such as noradrenergic, serotonergic and cholinergic cell types, makes them effective for abrogating the non-motor symptoms of PD.

• We advance the notion that stem cells, such as MSCs, capable of multiple lineage differentiation, secretion of growth factors and acting as therapeutic molecules for rescuing not only the dopaminergic system but other neurotransmitter systems as well, should be considered as a complement therapy to address the abnormal non-motor symptoms in addition to motor symptoms present in PD.